Histones as Exosome Membrane Proteins: Their Location and Regulation In Response to Cellular and Mitochondrial

Topic

Dr. Jonathan Gilthorpe from Umeå University, Sweden will talk about "Histones as Exosome Membrane Proteins: Their Location and Regulation In Response to Cellular and Mitochondrial" to the  Second World Congress on Targeting EVs, wich willbe held on October 15-16, 2025, in Valencia, Spain.

Summary

Associate Prof. Jonathan Gilthorpe from Umeå University, Sweden will speak about a novel location for histone proteins as a component of the extracellular vesicle (EV) membrane. Dr. Gilthorpe’s research is focused on understanding histone trafficking, the function of EV histones and their potential application for EV diagnostics and therapeutics.

Histones are conserved proteins with essential nuclear functions. When released from damaged cells as damage-associated molecular patterns (DAMPs), extracellular histones play important roles in inflammatory signalling. Elevated levels of extracellular histones are typically found in association with DNA and are pathogenic. However, histones are also released by healthy cells, where their functions are not understood.

They have found that histones are secreted as membrane associated proteins via the multivesicular body/intraluminal vesicle/exosome pathway. Histone secretion via exosomes is activated in response to cell stress, in association with smaller diameter EVs. EV histones lack most of the extensive post translational modification (PTMs) found in nuclear histones and do not require DNA for binding to the EV membrane.

The talk will focus on the pathways through which histones are routed to the MVB/exosome pathway, how histones bind to membranes as well as the role of mitochondrial stress in histone secretion.